The role of HIV infection in neurologic injury

The central nervous system (CNS) is a very challenging HIV-1 sanctuary, in which HIV-1 replication is established early on during acute infection and can persist despite potent antiretroviral treatments. HIV-1 infected macrophages play a pivotal role acting as vehicles for HIV-1 to spread into the brain, and can be the major contributor of an early compartmentalization. HIV-1 infection in CNS may lead to a broad spectrum of neurological syndromes, such as dementia, mild neurocognitive disorders, and asymptomatic impairment. These clinical manifestations are caused by the release of neurotoxins from infected cells (mainly macrophages), and also by several HIV-1 proteins, able to activate cell-signaling involved in the control of cellular survival and apoptosis. This review is aimed at highlighting the virological aspects associated with the onset of neurocognitive disorders and at addressing the novel therapeutic approaches to stop HIV-1 replication in this critical sanctuary.